1. Field of the Invention
The invention relates to a process for the fermentative production of S-adenosylmethionine.
2. Background Art
S-Adenosylmethionine (“SAM”) is an important methyl group donor in human metabolism and is used in the pharmaceutical field for the treatment of depression, diseases of the liver, and arthritis. A prior art process for SAM production comprises cultivation of yeasts (Schlenk and DePalma, J. Biol. Chem. 229, 1037-1050 (1957), Schlenk et al., Enzymologia 29, 283-298 (1965), Shiozaki et al., J. Biotechnol. 4, 345-354 (1986), Shiozaki et al., Agric. Biol. Chem. 53, 3269-3274 (1989)) in the presence of the precursor methionine and chromatographic purification of the SAM produced, after extraction from the cell lysate (U.S. Pat No. 4,562,149). SAM production by yeast is characterized by SAM being produced and stored intracellularly. In order to further process SAM, the cells must first be disrupted, as has been described, for example, in EP162323 (example 2) or in DE3329218 (example 1). Examples include chemical disruption methods, mechanical methods using a French press or high pressure homogenizers, and thermal processes (described in EP1091001, example 1).
In addition to SAM production by yeasts, the prior art also describes a bacterial SAM production process using Eherichia coli (E. coli), in which the bacteria excrete the SAM into the culture medium (EP 1 457 569 A1). Compared to the existing yeast processes, this fermentative SAM production process has a distinct advantage in that SAM is selectively secreted into the culture supernatant thereby simplifying the purification process. Since the culture supernatant contains only a few substances, secretion of SAM, therefore, already constitutes a first purification step facilitating further work-up. This process for extracellular SAM production utilizes a SAM synthetase.